62.Carcinoma of the colon. Characteristics according to the localization

Question 1

Carcinoma of the colon - Main points / intro

Answer 1

Although the majority of colorectal cancer is sporadic, several hereditary syndromes provide paradigms for the study of this disease.

Carcinoma colon is commonly adenocarcinoma. Very rarely adenosquamous, squamous carcinoma can occur

Question 2

Adenocarcinoma - Main Points

Answer 2

➢ Sigmoid colon (21%) is the most common site of malignancy after rectum (38%)

➢ In caecum it is 12% common

Question 3

Carcinoma of the colon - Etiology

Answer 3

Diet

Genetic

Question 4

Carcinoma of the colon - Dietary Etiology

Answer 4

▪ Red meat and saturated fat increase the incidence of colonic cancer.

▪ Cholesterol increases the bile acid concentration in the intestinal lumen which acts as cocarcinogen.

▪ High fibre diet protects the colon against cancer.

▪ Calcium in diet prevents colonic cancer by combining with bile salts and reducing bile salt concentration in the colon. It directly acts on the colonic mucosal cells to reduce their proliferative potential.

▪ Diet with lack of fibre increases the risk. Diet with high fat increases the risk.

▪ Dietary vitamins A, C, E and zinc reduces the risk.

Question 5

Carcinoma of the colon - Genetic etiology

Answer 5

▪ Carcinoma colon is more common in individuals with adenoma colon or with familial adenomatous polyposis (FAP), Gardner’s syndrome, Turcot’s syndrome.

▪ Relatives of colonic cancer patient have got 2–4 times increased risk of developing carcinoma of colon.

➢ Long standing ulcerative colitis, Crohn’s disease has high risk of colonic cancer. Crohn ‘s disease is a premalignant condition but not as much as ulcerative colitis.

➢ Alcohol and cigarette smoking increase the risk.

➢ Hereditary nonpolyposis colonic cancer (HNCC) has got high incidence (25%) of synchronous and metachronous growth, so total colectomy is needed.

➢ After cholecystectomy and ileal resection there is increased bile salts and so more prone for carcinoma colon.

➢ Radiation increases the risk (mucinous type).

➢ Ureterosigmoidostomy increases the risk by 100–500 times.

➢ Acromegaly may increase the risk.

Note: Aspirin, calcium and other NSAIDs protect against colonic cancer.

Question 6

Pathogenesis

Answer 6

Adenoma—carcinoma sequence:

Normal epithelium

5q initiates loss of APC gene

Hyperproliferative dysplasia occurs

DNA methylation

Early adenoma

12p activatES K-ras

Intermediate adenoma

18q initiates loss of DCC

late adenoma

17p initiates loss of p53

Carcinoma

Spread.

Question 7

Pathogenesis PART 2

Answer 7

80% of colorectal cancer arises from loss of heterozygosity (LOH) pathway.
➢ 20% of colorectal cancer develops from mutation from RER (Replication Error Repair) pathway wherein repair mechanism of DNA replication error is lost

Question 8

Pathogenesis part 3 - Types of colon cancer depending on etiology

Answer 8

Colonic cancer may be:
➢ Nonhereditary colon cancer
▪ It can be sporadic colon cancer—60%.

▪ It can be familial colon cancer—30%. Common in Ashkenazi – Jewish population.

➢ Hereditary colon cancer

▪ FAP.
▪ HNCC.

▪ Peutz Jeghers syndrome—2–3% risk of cancer colon.

▪ Cronkite—Canada syndrome.

▪ Juvenile polyposis syndrome - mutation of SMAD 4 gene is observed

Question 9

Types

Answer 9

➢ Annular (stenosing) type
▪ It is more common on left side.

▪ Here the growth spreads round the internal wall and so it often presents with intestinal obstruction.

➢ Ulcerative type: It is common on right side.

➢ Proliferative type: Common in right side. It is fleshy, bulky and polypoid. It is less malignant.

Question 10

Grading

Answer 10

Duke’s histological grading aka Morson-Dawson

▪ Grade I—low grade.

▪ Grade II—average grade.

▪ Grade III—high grade.

▪ Grade IV—anaplastic.

Carcinoma confined to muscularis mucosa does not metastasize.

Question 11

Spread

Answer 11

➢ Direct spread:
To bladder and ureters

Lymphatic spread:

▪ Growth through lymphatics spreads to pericolic, epicolic, intermediate and principal group of lymph nodes.

Blood spread:
▪ 40% of carcinoma colon spreads to liver via portal veins.

▪ Secondaries may be either solitary or multiple, present as liver with hard, umbilicated nodules.

Question 12

Clinical Presentation

Answer 12

➢ Occurs usually after 50 years. Familial type can present in younger age group. Common in males (M: F :: 3 : 2).

➢ Commonly present with loss of appetite and weight, anaemia, abdominal discomfort and mass per abdomen.

➢ 20% of cases present as an acute intestinal obstruction.

➢ 20% of colonic/colorectal cancer has stage IV disease at the time of first presentation.

Question 13

Clinical Presentation

Answer 13

➢ Occurs usually after 50 years. Familial type can present in younger age group. Common in males (M: F :: 3 : 2).

➢ Commonly present with loss of appetite and weight, anaemia, abdominal discomfort and mass per abdomen.

➢ 20% of cases present as an acute intestinal obstruction.

➢ 20% of colonic/colorectal cancer has stage IV disease at the time of first presentation.

Pericolic abscess/obstruction (15%)/perforation/ peritonitis may be the first presentation.

Question 14

Clinical Presentation for Right sided growths

Answer 14

Anaemia

Palpable mass in the right iliac fossa, which is not moving with respiration

Mobile, nontender, hard, well-localised with impaired resonant note.

Carcinoma of the caecum occasionally presents like acute appendicitis or intussusception with intestinal obstruction.

Question 15

Clinical Presentation for Left sided growths

Answer 15

Left sided growth presents with

Colicky pain

Constipation and diarrhoea

Palpable lump

Distension of abdomen due to subacute/chronic obstruction.

May present like complete
colonic obstruction.

Tenesmus, with passage of blood and mucus

Bladder symptoms may warn colovesical fistula.

Question 16

Diagnostic investigations

Answer 16

➢ Barium enema: Shows irregular filling defect and ‘apple core’ lesion (in left sided carcinoma). It also helps in finding colonic polyps

➢ Colonoscopy and biopsy confirm the diagnosis.

➢ Virtual colonoscopy (CT colonography) is also useful to visualize entire colon.

➢ US, to see secondaries in liver, peritoneum, lymph node status, rectovesical secondaries.

➢ CEA (carcinoembryonic antigen): CEA is primarily associated with colorectal cancers, but it can also increase significantly in pancreatic, gastric, lung, breast carcinomas.

➢ CT scan abdomen and pelvis—to see local spread, invasion, size and extent, stage, nodal status and liver secondaries.

➢ Left supraclavicular lymph node if palpable

➢ Occult blood in stool is the initial test for anaemia so need Hb%, PCV, haematocrit, ESR.

➢ LFT—mainly enzyme studies like AP, SGPT.

Question 17

Screening

Answer 17

➢ Faecal occult blood test (FOBT)—it is nonspecific test for peroxidase contained in haemoglobin.

➢ Flexible sigmoidoscopy—once in 5 years to identify the adenoma;

➢ Colonoscopy is the most accurate and most complete method for evaluating the entire colon. It allows identification of small polyps

➢ Air contrast barium enema (ACBE) detects polyps greater than 1 cm

➢ CT colonography

Question 18

Treatment

Answer 18

Right-sided early growth: Right radical hemicolectomy with ileo-transverse anastomosis

Left-sided early growth: Left radical hemicolectomy

Transverse colon growth: An extended right hemicolectomy with ileocolic anastomosis.

Multiple primaries - Total abdominal colectomy with ileorectal anastomosis

Liver secondaries - hemihepatectomy and Metastasectomy

Question 19

Owen Wangensteen’s Second look surgery

Answer 19

Owen Wangensteen’s Second look surgery- resect the residual or recurrent tumours

Question 20

Treatment for Recurrent Tumors

Answer 20

Adjuvant Therapy such as

Chemotherapy - done when there are Changes in CEA level.

Radiotherapy (RT) - if inoperable recurrent tumour